We propose to investigate physiological mechanisms that govern the release of vasopressin and opiomelanocortins at the peripheral (Project A), central (B) and cellular (C) level. In A we test the hypothesis that the hepatic portal vein may be a chemosensory (osmo- and pH-receptive) area involved in the neuroendocrine control of the blood circulation. By a combined physiological-morphological approach on anaethetized dogs or rats we attempt to reveal the areas and structures of the portal vein and central pathways that mediate responses of vasopressin, opiomelanocortins, ventilation, cardiac output, arterial pressure and superior mesenteric flow to local changes in osomolality and pH. In B television fluorescence microscopy of the epi-illuminated and in depth focused microcirculation within the rat median eminence tells us if blood cells and thus pituitary hormones may flow from pituitary gland to brain, a necessary condition for short-loop feed-back control. Long-term (4 weeks) co-cultures of hypothalamic and other brain explants with anterior pituitary tissue reveal sources of corticotropin and other releasing factors by their effect on anterior pituitary hormone release, an approach that adds different and new information to immunocytochemistry. Vasopressin of the external median eminence - a putative ACTH releasing factor - may differ in structure or precursor from neural lobe vasopressin. We test this hypothesis by reverse phase, high pressure liquid chromatography of vasopressin extracted from the external and internal median eminence and neural lobe, combined with radioimmunoassays for neurohypophysial hormones and corticoliberin. In C we investigate cellular actions of vasopressin and corticoliberin on a population enriched (60-70%) in anterior pituitary corticotrophs by cell sorting and ficoll gradient; in particular, we examine the role of ions (Ca, Na, K) cyclic nucleotides and calmodulin in the stimulated secretion of opiomelanocrotins and in prescursor processing, by molecular sieve, high pressure liquid chromatography and radioimmunoassays of ACTH, Beta-endorphin and Gamma3-MSH. The three projects (A, B, C) should give new insights in control and action of vasopressin and opiomelanocortins, hormones of general importance in the homeostasis of arterial pressure and water and salt metabolism.